Pulsations of engineered microvessels enhance solute clearance via heterogeneous strain-dependent poroelasticity

Abstract

Tissue homeostasis relies on the exchange of interstitial fluid between blood and tissues, as well as lymphatic drainage. In regions lacking conventional lymphatic vasculature, such as the central nervous system, the mechanisms governing interstitial fluid clearance remain debated, with vascular pulsatility proposed as a potential driver of interstitial fluid transport. Using a microvessel-on-chip platform that enables pulsatile pressure actuation and real-time visualization of deformation and interstitial solute dynamics in a tissue-mimetic collagen hydrogel, we investigated how pulsatile actuation regulates solute transport. Sinusoidal pressure stimulation produced a flattened but nearly symmetric deformation response in acellular lumens, whereas HUVEC-vascularized lumens exhibited pronounced asymmetry between expansion and retraction, accompanied by strain accumulation in the surrounding hydrogel. In vascularized systems, but not acellular controls, pulsatile actuation enhanced solute clearance and increased the cycle-averaged solute front velocity compared with constant-pressure actuation. To investigate the underlying mechanism, we developed a one-dimensional large-deformation poroelastic model of the vascularized bilayer. The model reproduced net directional fluid transport and showed that bilayer poromechanical heterogeneity combined with strain-dependent nonlinear permeability generates an influx-efflux asymmetry and net fluid flow. Together, these findings identify how pulsatile pressure within microvessels can generate directional interstitial fluid transport and enhance solute clearance, potentially contributing to tissue homeostasis.